Electrospray ionization is used to produce ions for mass spectrometry analysis including ions that are derived from relatively large complex molecules such as proteins and nucleic acid molecules. During the electrospray ionization procedure, a sample solution is exposed to an electrical field that charges the surface of the liquid and emerges from an electrospray tip or needle. A spray of finely dispersed charged droplets is thereby generated that is suitable for analysis by a mass spectrometer. The need for conducting high-throughput analysis of relatively small biological samples has led to the development of microfluidic chip devices for electrospray ionization applications.
Microfluidic chips are often constructed using well-known techniques employed in the semiconductor industry such as photolithography, wet chemical etching, and thin film deposition. These devices conveniently support the separation and analysis of sample sizes that are as small as a few nanoliters or less. In general, these chips are formed with a number of microchannels that are connected to a variety of reservoirs containing fluid materials. The fluid materials are driven or displaced within these microchannels throughout the chip using electrokinetic forces, pumps and/or other driving mechanisms. The microfluidic devices available today can conveniently provide mixing, separation, and analysis of fluid samples within an integrated system that is formed on a single chip.
There are numerous design alternatives to choose from when constructing an interface for microfluidic chips and electrospray ionization mass spectrometers. Some electrospray ionization interfaces include microfluidic chips that attempt to spray charged fluid droplets directly from the edge of the chip. But the accompanying solvent is known to wet much of the edge surface of the chip so as not to offer a high-stability spray for many applications. Other attempts to spray ionized particles directly from the edge of a microfluidic chip edge therefore rely on the formation of a hydrophobic surface that can yield improved spray results; however, even that often proves to be insufficiently stable. At the same time, adequate results can be also achieved with other chip devices that incorporate fused silica capillary needles or micro-machined or molded tips. In particular, some recent electrospray ionization designs incorporate small silicon etched emitters positioned on the edge of a microfluidic chip. While it is possible to generate a relatively stable ionization spray for mass spectrometric analysis with some of these microfluidic devices today, they generally require apparatus that is relatively impractical and economically unfeasible for mass production.
A high performance electrospray ionization device is therefore needed for mass spectrometry applications that can be economically produced using large scale manufacturing processes.